Tardive dyskinesia consists of abnormal, involuntary movements usually of oral facial musculature but often involving the trunk and extremities. There is no known cure for this involuntary movement disorder, and it is usually irreversible. Therefore, prevention is the presently known effective method for dealing with the problem. Tardive dyskinesia often occurs in geriatric patients who have been taking neuroleptic drugs. In recent years, the greater use of psychotropic drugs has aggravated the incidence of tardive dyskinesia.
The typical oral facial movements include puffing of the checks, grimacing, protrusion and licking of the tongue, and chewing movements of the jaw and frequent incessant blinking of the eyes. The abnormal movements are rhythmic and repetitive and may interfere with speech, salivation, chewing, and swallowing. The patient may not even be aware of their presence. Tardive dyskinesia usually appears after months or years of treatment with neuroleptic drugs but it may develop after only a few weeks of such treatment. All neuroleptic drugs may cause tardive dyskinesia. However, the low-dose high potency drugs which produce the greatest degree of blockage, and thus a greater degree of extra pyramidal side effects are the most likely to cause tardive dyskinesia. Such high potency drugs include the phenothiazines, the thioxanthenes, the butyrophenones, the behzodiazepines and the dihydroindolones. The increasing use of neuroleptic drugs in geriatric care facilities has resulted in dramatic increase in the incidence of tardive dyskinesia. See Geriatrics, Volume 34, Number 7, pages 59-66, July 1979, by Harcourt Brace Jovanovich, Inc.
It has recently been discovered that cholinergic as well as dopaminergic systems may be involved in extrapyramidal movement disorders such as tardive dyskinesia. This lead to the investigation of anticholinergic drugs. It is reported in American Journal of Psychiatry, Volume 134, Number 7, July 1977, pages 769-774 that the use of physostigmine injections and choline have a positive therapeutic effect on tardive dyskinesia. Although the data presented is not clear, tests have shown that physostigmine injections reduce tardive dyskinesia movements in from 20% to 80% of patients suffering from tardive dyskinesia.
Further tests have been made with lecithin. Preliminary tests have indicated that patients with tardive dyskinesia who were treated by ingesting lecithin (phosphatidyl choline) over a 14 day period experienced significant improvement. See Science News, Volume 116, page 393, Dec. 8, 1979.
Recently, it has been demonstrated that injections of physostigmine salicylate have relieved the symptoms of tardive dyskinesia. However, the use of injectable forms of physostigmine compositions is not practical for useful therapy because the action of the physostigmine salt has a duration of not longer than 2 hours. The physostigmine salt is thus metabolized in the human body rapidly, in about 60-120 minutes. For treatment of tardive dyskinesia this would require injection every 2 hours, which treatment is not considered practical by physicians.
Physostigmine was first isolated in 1864 by Jobst and Hesse after it was originally introduced into England in the form of the calabar bean, in 1840, by Daniell, a British medical officer. During the last century, physostigmine has been used as a treatment for glaucoma and in post-operative ileus, and in the reversal of atropine-induced coma. More recently, physostigmine has been used effectively as an antidote to several drugs possessing central anticholinergic properties. See Journal Of The American College Of Emergency Physicians and University Association For Emergency Medical Services, June, 1976, Volume 5, Number 6, pages 436-439. Pediatrics, Volume 52, Number 3, September, 1973 discusses the use of physostigmine compounds such as physostigmine salicylate in the treatment of anticholinergic poisoning. The use of physostigmine in the treatment of anticholinergic poisoning is also discussed in Journal of The American College Of Emergency Physicians And University Association For Emergency Medical Services, Volume 5, Number 2, February, 1976, pages 125-127 wherein it is noted that drugs with anticholinergic effects are readily available to the public by prescription and over-the-counter and are increasingly the subject of abuse by the patients. This article discusses the use of physostigmine as an emergency antidote. The Journal Of The American College Of Emergency Physicians And University Associations For Emergency Medical Services, Volume 5, Number 6, June, 1976, pages 443-445 also discusses the use of physostigmine in the treatment of tricyclic antidepressant overdoses. The use of physostigmine compounds to reverse the effect of scopolamine in parturients is described in the American Journal of Obstetrics And Gynecology, Volume 116, Number 3, pages 326-329, June 1, 1976 and in The Journal Of International Anesthesia Research Society, Volume 55, Number 4, July-August, 1976. Thus, the use of physostigmine compounds to counteract the undesirable anticholinergic effect of many useful drugs has been known for a number of years and is growing in utilization by physicians.